Cell death & disease · 2023
Transglutaminase Type 2-MITF axis regulates phenotype switching in skin cutaneous melanoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Muccioli Silvia, Brillo Valentina, Varanita Tatiana, Rossin Federica, Zaltron Elisabetta, Velle Angelo, Alessio Giorgia, Angi Beatrice, Severin Filippo, Tosi Anna, D'Eletto Manuela, Occhigrossi Luca, Falasca Laura, Checchetto Vanessa, Ciaccio Roberto, Fascì Amelia, Chieregato Leonardo, Rebelo Ana Paula, Giacomello Marta, Rosato Antonio, Szabò Ildikò, Romualdi Chiara, Piacentini Mauro, Leanza Luigi
Аннотация
Skin cutaneous melanoma (SKCM) is the deadliest form of skin cancer due to its high heterogeneity that drives tumor aggressiveness. Melanoma plasticity consists of two distinct phenotypic states that co-exist in the tumor niche, the proliferative and the invasive, respectively associated with a high and low expression of MITF, the master regulator of melanocyte lineage. However, despite efforts, melanoma research is still far from exhaustively dissecting this phenomenon. Here, we discovered a key function of Transglutaminase Type-2 (TG2) in regulating melanogenesis by modulating MITF transcription factor expression and its transcriptional activity. Importantly, we demonstrated that TG2 expression affects melanoma invasiveness, highlighting its positive value in SKCM. These results suggest that TG2 may have implications in the regulation of the phenotype switching by promoting melanoma differentiation and impairing its metastatic potential. Our findings offer potential perspectives to unravel melanoma vulnerabilities via tuning intra-tumor heterogeneity.